Cytochrome P450 constitutes a large gene family of enzymes that participate in the oxidative activation and/or deactivation of a wide range of xenobiotics, including many potential carcinogens and several anticancer drugs (Guengerich and Shimada (1991) Chem. Res. Toxicol. 4:931; Gonzalez and Gelboin (1994) Drug Metab. Rev. 26:165; Kivisto et al. (1995) Br. J. Clin. Pharmacol. 40:523).
The human CYP1 gene family, one of the major P450 families, consists of three individual forms classified into two sub-families. CYP1B1, a member of one sub-family, is 543 amino acids in length. It is structurally distinct from the two members of the CYP1A2 subfamily (Tang et al., J. Biol. Chem. (1996) 271:28324).
Studies of various types of cancer, including breast cancer, esophageal cancer and soft tissue sarcomas, have shown that there may be tumor-specific expression of a CYP1B1 form of P450 (see Murray et al. (1991) Br. J. Cancer 63:1021; Murray et al. (1993) J. Pathol. 171:49; Murray et al. (1994) Gut 35:599). Immunohistochemistry studies of CYP1B1 show a strong immunoreactivity for several different types of tumors (bladder, breast, colon, kidney, lung, esophagus, ovary, skin, stomach, uterus, bone and connective tissue, lymph node, brain, and testis) (see WO 97/12246, herein incorporated by reference).